Interaction between respiratory and heart activities occurs anywhere within the thoracic cavity and can be extracted reliably from signals obtained directly within central blood vessels such as the aorta.
It is known in the art that either the positive pressures applied during mechanical ventilation or the negative intra-thoracic pressures during spontaneous breathing induce cyclic changes in left ventricular stroke volumes. The more both the right and the left ventricle become preload dependent, the more likely they will respond positively to the administration of intravascular fluids. As described by Michard et al. in their review article (Michard et al. Crit Care 2000, 4:282-289) mainly the Frank-Starling relationship determines a living being's response to volume expansion. Clinical data demonstrate that respiratory-induced variations in arterial pulse pressure (PPV), in systolic pressure (SPV), but more importantly in left ventricular stroke volume (SVV), which can be determined by the surrogate parameters of Doppler aortic blood flow velocity, can be used to detect biventricular preload dependence, and hence be exploited as surrogates for fluid responsiveness in living beings, particularly in critically ill patients. Although the names of these different parameters (PPV and SVV) do not directly elude to them as being direct or indirect measures of fluid responsiveness, a newly introduced fluid responsiveness index (FRI) does this in an explicitly way (see U.S. 2008/0033306).
Despite the fact that the described parameters of heart-lung interaction are of utmost clinical importance, to date none of them can be measured non-invasively. While U.S. patent 2008/0033306 suggests more advanced and sophisticated algorithms to extract rather reliable information on heart-lung-interaction and fluid responsiveness in ventilated as well as non-ventilated patients, it remains entirely depend on signals obtained from invasive pressure measurements in central arteries such as the aorta, the femoral or brachial arteries. Thus, while the proposed approach to a more robust determination of fluid responsiveness has to be applauded, it does not address the underlying problem of invasiveness.
A first non-invasive approach to assess heart-lung interactions via a non-invasive technique is that proposed by Masimo (Irvine, US) based on the analysis of photo-plethysmographic time series at peripheral measurement sites such as the finger tip. Masimo introduced the so-called Pleth Variability Index (PVI) (Cannesson et al, British Journal of Anesthesia 2008; 101: 200-206). Unfortunately, PVI relies on the analysis of pulsatility signals from very distal arteries of the muscular type. The characteristics of these arteries, however, are substantially different from those of central arteries such as the aorta. Thus, by nature of the approach PVI can provide nothing else but non-central estimates of heart-lung interaction: local vasoconstriction phenomena are prone to bias such estimates, especially in hemodynamically critical situations in which the information on fluid responsiveness is needed the most. Thus, while the proposed approach addresses the non-invasiveness, the fact that it relies on distal photo-plethysmographic signals constraints its application: it does not provide a method for analyzing central hemodynamics.
Control of cardiovascular instability is crucial when treating critically ill patients. Clinical assessment and treatment of intravascular fluid status are usually guided by arterial filling pressures. However, the clinical value of these pressure-related filling parameters in states of critical illness and during positive pressure ventilation has been questioned repeatedly and fundamentally: central venous and pulmonary artery occlusion pressures poorly predict the hemodynamic response to a fluid challenge. Pressure-based concepts are inferior to volume-based concepts as they are substantially influenced by intra-thoracic pressures. Thus, they do not allow inferences on cardiac preload. Functional hemodynamic parameters derived from invasive arterial pressure or flow signals, quantifying the interactions between heart and lungs, known as heart-lung interaction (HLI), pulse pressure variations (PPV), left ventricular stroke volume variations (SVV) or systolic pressure variations (SPV) have shown to be clinically superior. However, current methods for determining such parameters are usually performed in the time domain rendering them susceptible to artifacts and noise. Thus, more robust means of calculating these parameters are highly desirable.
Furthermore, the above mentioned parameters can be calculated reliably only from signals which need to be obtained by invasive catheters, with their associated risks and complications. Therefore, not only more robust but also less invasive means of obtaining reliable predictors of fluid responsiveness or heart-lung interaction are needed.
EIT is a non-invasive functional imaging technology that measures changes in bio-impedance at skin electrodes to reconstruct sequences of cross-sectional functional images. The methodology of EIT can be used for monitoring a patient's responsiveness to intravascular volume loading as the changes in bio-impedance are directly related to changes in stroke volumes, which result from changes in cardiac preload whereas pressure-based parameters such as PPV or SPV reflect only the results of such volume changes but not their underlying cause. However, in EIT more than 90% of the signal amplitude at the thoracic surface is due to breathing. Therefore, it becomes challenging to exploit the small ventilation-modulated variations in stroke volume, which account for no more than 1 to 2% of the total signal strength. Conventional EIT post-processing techniques are unable to analyze such low-amplitude events.
To date, assessing SVV in living beings, particularly in critically ill patients with adequate accuracy can only be achieved by obtaining blood flow or pressure signals within the most central arteries. Attempts of using signals from less invasive peripheral arteries, or even from noninvasive pulse oximetry showed promising results under stable hemodynamic conditions, but unfortunately failed during cardiovascular instability. The reasons are obvious: whenever the hemodynamic status becomes unstable, the vascular tone of peripheral arteries is adapted either as a result of endogenous counter-regulation or of treatment by vasoactive medication. Additionally, reduced peripheral perfusion, as in shock further reduces signal quality, thereby limiting even more the usefulness of the less invasive approaches currently en vogue.
It is an aim of the present invention to obviate, or mitigate, at least some of the above-mentioned disadvantages.